Hardwiring the Nervous System

Before the brain can produce thought, control limbs or make us flinch in pain, innumerable connections must be built between the more than one hundred billion cells that make up the central nervous system.

Figuring out exactly how this occurs drives the research of Samantha Butler, an assistant professor of biological sciences in USC College, who focuses on how the brain and spinal cord get wired up.

“We are just beginning to understand how these neural networks are built,” says Butler, who arrived at USC College last winter from Columbia University’s Center for Neurobiology and Behavior. “The idea is to look at how these are set up to begin with, in the embryo,” she says.

Understanding how the body builds new neural connections would be key to any future scheme to repair damaged neural networks, such as those found in spinal cord lesions — a leading cause of paralysis.

Butler studies how axons — the threadlike extensions of neurons that transmit signals from a neuron — hook up with other neurons. During this carefully orchestrated process, axons must grow thousands of times the width of a neuron to form the stereotypical pattern encoded in the genetic blueprint.

Work over the last 20 years has shown that, to navigate this long and vitally important journey, axons rely on a series of molecular cues.

These molecules may attract the tip of the axon in one direction or repel it from another direction, guiding the axon to grow toward precise targets in the developing spinal cord and brain, Butler says.

Butler is best known for demonstrating that BMPs, members of a family of growth factors, can repel axons. Although BMPs had been studied for years by molecular and developmental biologists, Butler was the first to show their important role in axon guidance — a key finding that spawned new interest in the BMP family of proteins among neuroscientists.

Butler continues to search for other so-called chemorepellents and chemoattractants, as well as looking at molecular and cellular events involved in the process. Eventually, she aims to understand how the many guidance cues work together to direct axons on the right path in the spinal cord.

“The practical aspect of this work, which would be dependent on parallel advances in neural stem cell research and medicine, is to see if we could somehow use similar compounds to help re-establish neural pathways after injury,” she says.